[6-[6-(trifluoromethyl)pyridin-3-yl]pyrimidin-4-yl] methanamine hydrochloride | 1590398-46-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: [6-[6-(trifluoromethyl)pyridin-3-yl]pyrimidin-4-yl] methanamine hydrochloride
• 英文别名: [6-[6-(trifluoromethyl)-3-pyridyl]pyrimidin-4-yl]methylamine hydrochloride；(6-(6-(Trifluoromethyl)pyridin-3-yl)pyrimidin-4-yl)methanamine hydrochloride；[6-[6-(trifluoromethyl)pyridin-3-yl]pyrimidin-4-yl]methanamine;hydrochloride
• CAS: 1590398-46-1
• 化学式: C₁₁H₉F₃N₄*ClH
• 分子量: 290.675
• InChiKey: AMNQMWBKXWYKTF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.44
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  64.7
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [6-[6-(trifluoromethyl)pyridin-3-yl]pyrimidin-4-yl] methanamine hydrochloride 在 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成 (2S)-1-(4-fluorophenyl)sulfonyl-N-[[6-[6-(trifluoromethyl)-3-pyridyl]pyrimidin-4-yl]methyl]pyrrolidine-2-carboxamide
  参考文献：
  名称：

  Discovery of a Potent (4R,5S)-4-Fluoro-5-methylproline Sulfonamide Transient Receptor Potential Ankyrin 1 Antagonist and Its Methylene Phosphate Prodrug Guided by Molecular Modeling

  摘要：

  Transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel expressed in sensory neurons where it functions as an irritant sensor for a plethora of electrophilic compounds and is implicated in pain, itch, and respiratory disease. To study its function in various disease contexts, we sought to identify novel, potent, and selective small-molecule TRPA1 antagonists. Herein we describe the evolution of an N-isopropylglycine sulfonamide lead (1) to a novel and potent (4R,SS)-4-fluoro-S-methylproline sulfonamide series of inhibitors. Molecular modeling was utilized to derive low-energy threedimensional conformations to guide ligand design. This effort led to compound 20, which possessed a balanced combination of potency and metabolic stability but poor solubility that ultimately limited in vivo exposure. To improve solubility and in vivo exposure, we developed methylene phosphate prodrug 22, which demonstrated superior oral exposure and robust in vivo target engagement in a rat model of AITC-induced pain.

  DOI：

  10.1021/acs.jmedchem.8b00117
• 作为产物：
  描述：

  tert-butyl N-([6-[6-(trifluoromethyl)pyridin-3-yl]pyrimidin-4-yl]methyl)carbamate 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 2.0h， 以80%的产率得到[6-[6-(trifluoromethyl)pyridin-3-yl]pyrimidin-4-yl] methanamine hydrochloride
  参考文献：
  名称：

  [EN] BICYCLIC PROLINE COMPOUNDS
  [FR] COMPOSÉS DE PROLINE BICYCLIQUES

  摘要：

  本发明涉及化合物的结构式(I)及其盐。此外，本发明还涉及制备和使用结构式(I)化合物的方法，以及含有这些化合物的药物组合物的方法。这些化合物可能对治疗由TRPA1介导的疾病和症状，如疼痛，具有用处。

  公开号：

  WO2018015410A1

文献信息

• HETEROCYCLIC SULFONAMIDE DERIVATIVE AND MEDICINE COMPRISING SAME
  申请人：EA PHARMA CO., LTD.

  公开号：US20160332999A1

  公开（公告）日：2016-11-17

  The present invention provides a compound represented by the formula (I): wherein each symbol is as defined in the DESCRIPTION, or a pharmaceutically acceptable salt thereof. The compound has a superior TRPA1 antagonist activity, and can provide a medicament useful for the prophylaxis or treatment of diseases involving TRPA1 antagonist and TRPA1.

  本发明提供了一种由公式(I)表示的化合物： 其中，每个符号如说明书中所定义，或者其药用可接受的盐。该化合物具有优越的TRPA1拮抗剂活性，并且可以提供一种用于预防或治疗涉及TRPA1拮抗剂和TRPA1的疾病的药物。
• [EN] SUBSTITUTED SULFONAMIDE COMPOUNDS<br/>[FR] COMPOSÉS DE SULFONAMIDE SUBSTITUÉS
  申请人：HOFFMANN LA ROCHE

  公开号：WO2014049047A1

  公开（公告）日：2014-04-03

  The invention is concerned with the compounds of formula (I), and salts thereof, wherein X, Y, Z, R1, R2, R3, R3, R4, R5 and R6 are defined in the detailed description and claims. In addition, the present invention relates to methods of manufacturing and using the compounds of Formula (I) as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.

  本发明涉及公式(I)的化合物及其盐，其中X、Y、Z、R1、R2、R3、R3、R4、R5和R6在详细描述和权利要求中定义。此外，本发明还涉及制造和使用公式(I)化合物的方法，以及含有此类化合物的药物组合物。这些化合物可能对治疗由TRPA1介导的疾病和状况，如疼痛，有益。
• [EN] SUBSTITUTED HETEROCYCLIC SULFONAMIDE COMPOUNDS USEFUL AS TRPA1 MODULATORS<br/>[FR] COMPOSÉS DE SULFONAMIDE HÉTÉROCYCLIQUES SUBSTITUÉS UTILES COMME MODULATEURS DE TRPA1
  申请人：HOFFMANN LA ROCHE

  公开号：WO2015052264A1

  公开（公告）日：2015-04-16

  The invention is concerned with the compounds of formula I or II: and salts thereof. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula I or II as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.

  本发明涉及式I或II的化合物及其盐。此外，本发明还涉及制备这些化合物的方法以及使用这些化合物的方法，以及含有这些化合物的药物组合物。这些化合物可能对治疗由TRPA1介导的疾病和状况，如疼痛，具有用途。
• CYCLOPROPANE DERIVATIVE AND DRUG CONTAINING SAME
  申请人：EA PHARMA CO., LTD.

  公开号：EP3330266A1

  公开（公告）日：2018-06-06

  A compound represented by the formula (I): wherein each symbol is as defined in the DESCRIPTION, or a pharmaceutically acceptable salt thereof has superior TRPA1 antagonist activity, and the compound or a pharmaceutically acceptable salt thereof is useful for the prophylaxis or treatment of diseases involving TRPA1 antagonist and TRPA1.

  化合物的化学式为(I)： 其中每个符号的定义如描述中所定义， 或其药学上可接受的盐具有优越的TRPA1拮抗活性，该化合物或其药学上可接受的盐对涉及TRPA1拮抗剂和TRPA1的疾病的预防或治疗是有用的。
• [EN] AMIDS SUBSTITUTED INDAZOLE DERIVATIVEES AS PLOY (ADP-RIBOSE) POLYMERASE INHIBITORS<br/>[FR] DÉRIVÉS D'INDAZOLE À SUBSTITUTION AMIDE EN TANT QU'INHIBITEURS DE POLY (ADP-RIBOSE) POLYMÉRASE
  申请人：BETTA PHARMACEUTICALS CO LTD

  公开号：WO2015051766A1

  公开（公告）日：2015-04-16

  The present invention relates to amide substituted indazoles and benzotriazoles which are inhibitors of the enzyme poly (ADP-ribose) polymerase (PARP), previously known as poly (ADP-ribose) synthase and poly (ADP-ribosyl) transferase. The compounds of the present invention are useful as mono-therapies in tumors with specific defects in DNA-repair pathways, as enhancers of certain DNA-damaging agents such as anticancer agents and radiotherapy, for reducing cell necrosis (in stroke and myocardial infarction), regulating inflammation and tissue injury, treating retroviral infections, and protecting against the toxicity of chemotherapy.

  本发明涉及酰胺取代的吲唑和苯并三唑，它们是酶聚(ADP-核糖)聚合酶（PARP）的抑制剂，以前被称为聚(ADP-核糖)合酶和聚(ADP-核糖基)转移酶。本发明的化合物可用作特定DNA修复途径缺陷肿瘤的单一治疗方法，作为某些DNA损伤药物如抗癌药物和放疗的增效剂，用于减少细胞坏死（在中风和心肌梗死中），调节炎症和组织损伤，治疗逆转录病毒感染，以及保护免受化疗毒性的影响。